Agalates, tablets 0.5 mg 8 pcs

Pharmacotherapeutic group: dopamine receptor agonist
ATC code: G02CB03.
PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
Cabergoline is a synthetic ergot alkaloid, ergoline derivative, a long-acting dopamine agonist that inhibits prolactin secretion. The mechanism of action of cabergoline includes stimulation of central hypothalamic dopaminergic receptors. In doses higher than those required for inhibition of prolactin secretion, the drug induces central dopaminergic effect, which is caused by stimulation of dopamine D2-receptors. The action of the drug is dose-dependent. Decrease of prolactin in blood is usually observed after 3 hours and remains during 2-3 weeks, in this connection a single dose of the preparation is usually enough to suppress milk secretion. When hyperprolactinemia is treated, blood prolactin levels normalize after 2-4 weeks of using the drug in an effective dose. Normal prolactin levels may persist for several months after withdrawal of the drug.

Cabergoline is highly selective and has no effect on basal secretion of other pituitary hormones and cortisol. The only pharmacodynamic effect unrelated to the therapeutic action is a decrease in arterial blood pressure (BP). The maximum hypotensive effect usually develops 6 hours after a single drug administration; the degree of BP reduction and the frequency of development of the hypotensive effect are dose-dependent.

Pharmacokinetics

Intake
After oral administration, cabergoline is rapidly absorbed from the gastrointestinal tract (GIT). Maximal concentration in blood plasma is reached within 0.5-4 h.
Food has no effect on absorption or distribution of cabergoline.

Distribution
Binding of cabergoline (at a concentration of 0.1-10 ng/ml) to plasma proteins is 41-42%.

Metabolism
Metabolites of cabergoline were detected in the urine: 6-allyl-8β-carboxy-ergoline in an amount of 4-6% of the dose taken, as well as three other metabolites with a total of less than 3%. All metabolites inhibit prolactin secretion to a much lesser degree (compared to cabergoline).

Elimination
Cabergoline has long half-life: T1/2 was 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia.
With this half-life the equilibrium state is reached after 4 weeks. In the urine and feces 18% and 72% of the administered dose were found, respectively. The urinary content of unchanged cabergoline is 2-3%.
Pharmacokinetics are linear up to a dose of 7 mg/day.
Preclinical safety data
As shown in preclinical studies, cabergoline is safe over a significant dose range and has no teratogenic, mutagenic or carcinogenic effects.

Indications

Active ingredient

Composition

How to take, the dosage

Cabergoline is taken orally preferably with meals.

Adults

Treatment of disorders associated with hyperprolactinemia. The recommended starting dose is 0.5 mg per week in one or two doses (e.g., Monday and Thursday). The dosage is increased gradually, usually by 0.5 mg/week at 1 month intervals until optimal therapeutic effect is achieved. The maximum daily dose should not exceed 3 mg.

The maintenance dose is 1 mg/week (0.25-2 mg/week); in selected cases in patients with hyperprolactinemia, up to 4.5 mg/week.

When using Agalates at doses above 1 mg/week, it is recommended that the weekly dose be divided into 2 or more doses depending on tolerance.

For suppression of physiological postpartum or established lactation: the recommended dose is 1 mg once within the first 24 hours after birth.

Application in patients with impaired hepatic or renal function

Information is provided under “CONTRAINDICATIONS”. and SPECIAL CONDITIONS.

Application in patients over 65 years of age

In view of the indications for use, experience with cabergoline in patients over 65 years of age is limited. The available data suggest that there is no specific risk.

Interaction

The effect of macrolide antibiotics on plasma levels of cabergoline when used together has not been studied. Taking into account the possibility of increasing the level of cabergoline, the drug is not recommended to use in combination with macrolides.

The mechanism of action of cabergoline is related to direct stimulation of dopamine receptors; therefore, it should not be used in combination with dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes, metoclopramide).

There is no information about interactions of cabergoline with other ergot alkaloids; however, long-term use of this combination is not recommended.

With regard to the pharmacodynamics (hypotensive effect) of cabergoline, interactions with blood pressure lowering drugs must be taken into consideration.

In clinical studies in patients with Parkinson’s disease no pharmacokinetic interaction with levodopa or selegiline was found. Pharmacokinetic interactions with other drugs cannot be predicted based on the available information about the metabolism of cabergoline.

Special Instructions

To open the bottle, first press on the cap, then rotate it as shown on the cap. Do not remove the silica gel pouch from the vial and do not ingest.

The data on the efficacy and safety of Agulates in patients with hepatic or renal impairment are limited. In patients with severe hepatic impairment (Child-Pugh class C), Agalates should be used in lower doses if long-term therapy is necessary.

The pharmacokinetics of cabergoline do not change significantly with moderate to severe renal impairment. It has not been studied in patients with terminal renal failure or on hemodialysis. Therefore, Agalates should be used with caution in these patients. The effect of alcohol on the overall tolerability of Agalates has not been established.

The use of Agalates may cause symptomatic arterial hypotension, especially when combined with blood pressure lowering drugs. It is recommended that BP be measured regularly in the first 3 to 4 days after the start of treatment.

The long-term use of Agalates and other ergot derivatives that are active against serotonin 5NT2B receptors increases the risk of fibrotic and serous inflammatory disease, such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, involvement of one or more heart valves (aortic, mitral, tricuspid), retroperitoneal fibrosis. Withdrawal of Agalates for these conditions resulted in improvement.

All patients should be fully evaluated before starting Agalates for long term therapy to detect cardiac valve disease, lung function and renal function to prevent a worsening of the disease course. Increased sedimentation rate of erythrocytes (sedimentation rate) has been noted in patients with pleural effusions/fibrosis, therefore, chest radiographs should be performed if there is elevated sedimentation rate without obvious clinical signs, and plasma creatinine concentration should be determined.

Long-term treatment with Agalates may gradually progress to fibrosis, therefore symptoms such as dyspnea, shortness of breath, cough, chest pain, low back pain, swelling of lower extremities, signs of retroperitoneal fibrosis (low back pain, malaise), heart failure should be monitored during treatment.

After initiation of Agalates therapy, the condition of cardiac valves should be monitored and an echocardiographic (EchoCG) examination should be performed for the first time 3-6 months after initiation of therapy to prevent fibrotic disorders. The frequency of EchoCG monitoring is then determined by the physician individually for each patient, but at least once every 6-12 months.

If there is worsening valve regurgitation, narrowing of the lumen, or thickening of the valve wall, Agalates therapy should be discontinued.

Drowsiness and episodes of “falling asleep” may occur with Agalates, especially in patients with Parkinson’s disease. Effects on driving and operating ability.

Agalates has been associated with increased libido, hypersexuality, and a pathological urge to gamble. These symptoms were reversible and disappeared with dose reduction or discontinuation of Agalates.

Hyperprolactinemia associated with amenorrhea and infertility may be associated with pituitary tumors, so pituitary function testing should be done before starting Agalates therapy.

We recommend checking serum prolactin levels every month, as normal prolactin concentrations are maintained for 2-4 weeks after an effective therapy regimen has been achieved.

After withdrawal of Agalates hyperprolactinemia usually occurs again. However, some patients experience a persistent decrease in prolactin concentrations for several months.

The use of Agalates restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur before menstruation resumes, pregnancy tests are recommended during amenorrhea, and after menstrual cycle recovery, in all cases of a delay of more than 3 days. For women who are not planning a pregnancy, effective non-hormonal contraception should be used during and after treatment with Agalates. Women planning to become pregnant are advised to conceive not earlier than 1 month after discontinuation of Agalates.

Effects on driving and operating machinery

Patients should be informed about the need for caution when driving or operating machinery. Patients who have already experienced drowsiness and/or episodes of sudden falling asleep during treatment with Agalates should avoid driving or other activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

Postpartum or uncontrolled arterial hypertension; hypersensitivity to cabergoline, other ergot alkaloids, or any drug component; severe hepatic impairment; pulmonary adverse events such as pleurisy or fibrosis (including a history) associated with dopamine agonists; psychosis (including a history) or risk of developing it; Pregnancy and pre-eclampsia and eclampsia developed against it; breastfeeding period; children under 16; cardiac valve defects after long-term therapy with cabergoline confirmed by echocardiography; concomitant use with macrolide antibiotics; lactose intolerance; lactase deficiency; glucose-galactose malabsorption syndrome.

WARNING

. Patients with cardiovascular disease, arterial hypotension, Raynaud’s syndrome, peptic ulcers or gastrointestinal bleeding, somnolence, sudden onset of sleep, patients with end-stage renal failure or on hemodialysis, patients over 65; long-term treatment with cabergoline.

Side effects

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very frequently – at least 10%; frequently – at least 1%, but less than 10%; infrequently – at least 0.1%, but less than 1%; rarely – at least 0.01%, but less than 0.1%; very rarely (including isolated cases) – less than 0.01%.

On the immune system: infrequent – hypersensitivity reaction, skin rash.

Blood and lymphatic system disorders:infrequent – erythromelalgia.

From the nervous system: often – hallucinations, sleep disorders, confusion, dizziness, dyskinesia, increased libido, headache, drowsiness, depression; infrequent – hyperkinesis, psychotic disorder, delirium, paresthesia, transient hemianopsia, fainting; very rarely – sudden sleep attack, pathological craving for gambling.

Cardiovascular system disorders:often – postural hypotension, angina pectoris, heart valve lesions (including regurgitation), pericarditis, pericardial effusion, “flushes”, palpitations, peripheral edema.

Gastrointestinal disorders:very frequently – nausea, abdominal pain; frequently – dyspepsia, vomiting, gastritis, constipation; rarely – pain in epigastric region; very rarely – retroperitoneal fibrosis.

In the respiratory system: frequent – dyspnea; infrequent – pleural effusion, pulmonary fibrosis, nasal bleeding.

Others:often – asthenia, weakness, impaired liver function, mammary gland pain, visual impairment; very rarely – cramps in the muscles of the lower extremities, increased creatine phosphokinase activity.

Overdose

Pregnancy use

The drug is contraindicated in pregnancy and lactation.

Pregnancy should be excluded before starting to take the drug. It is recommended to avoid pregnancy for at least 1 month after discontinuation of treatment. There are limited data on the use of the drug during pregnancy obtained during the first 8 weeks after conception. Cabergoline use has not been associated with an increased risk of abortion, premature birth, multiple pregnancies, or congenital abnormalities. No other data are available to date.

There have been no direct or indirect adverse effects of cabergoline on pregnancy, embryo/fetal development, labor or postnatal development in animal studies.

In view of the limited experience with the use of cabergoline in pregnancy, the drug should be discontinued if pregnancy is planned. If pregnancy occurs during treatment, cabergoline should be immediately withdrawn. Due to the possibility of expansion of a pre-existing tumor, signs of pituitary enlargement in pregnant women should be monitored.

Because cabergoline suppresses lactation, the drug should not be administered to mothers who prefer to breastfeed their infants. Breastfeeding should be stopped during treatment with cabergoline.

Similarities